Scientists Are Using Targeted Light to Help the Immune System Track Down Tumors

We fight cancer in a variety of ways, but no matter whether drugs, biologics, or our immune cells are part of the battle, they can do a better job fighting back cancer if we can help them find the tumors.

Scientists from the University of Rochester Medical Center (URMC) have developed a couple of simple ways that light and optics can be used to improve cancer treatment. Their discovery was published online in the journal Nature Communications.

The Promise of Immunotherapy

The field of cancer treatment is progressing rapidly. Great strides have been made that have taken us from using drugs that kill many healthy bystander cells in their quest to kill the cancer cells, to techniques that boost our own immune system's role in killing cancer.

Instead of directly killing cancer cells, immunotherapy tells the immune system to act in certain ways by stimulating T lymphocytes to attack the disease, but this therapy can cause immune cells to underreact or overreact.

One newer immune therapy is adoptive cell transfer. This technique uses a patient's own T lymphocytes. The patient's blood is drawn and, in the lab, scientists find the lymphocytes that react with the patient's tumor. Then they isolate just those cells, multiply them, and give them back to the patient in a transfusion.

This therapy has worked well for people with cancer of the blood, like malignant melanoma, but not so well for people with solid tumors.

Solid tumors can create an environment around them that inhibits the immune response and keep T cells from getting close enough to attack — specifically activating a population of cells called T regulatory cells. Those T regulatory cells try to keep the immune system in check by not letting too many cells get killed in an immune response, i.e., they regulate the response.

The T lymphocytes needed to kill cancer are called cytotoxic T lymphocytes. Under control of a tumor, T regulatory cells send signals that keep cytotoxic T lymphocytes from responding to cancer. Scientists believe this is why the cells put back into the patient in an adoptive cell transfer haven't worked as well on solid tumors.

Illustration of a T lymphocyte (animation viewable [http://blausen.com/en/video/white-blood-cell-lymphocyte-t-cell/ here]).

In general, only 40% of patients receiving immunotherapy get a good response to the treatment.

In theory, and in practice, immunotherapy makes use of our body's ready-made response to cancer when it shows up in our body, but it can use some help to boost its effectiveness. That's where the research from the URMC, led by Minsoo Kim, a professor of microbiology and immunology, comes in.

Using Light to Guide the Way

Kim and his team are pursuing two lines of investigation, both using light to get killer T lymphocytes to cancer cells where they can fight the tumor. Both systems capitalize on the fact that targeted light stimulation of calcium in T killer cells increases their ability to kill cancer cells.

The scientists found that a molecule called channelrhodopsin from algae is light sensitive and it could be put into cells used in an adoptive cell transfer procedure — the patient's killer T cells that are specially made to kill certain cancer cells.

When the cells were mixed in a test tube with the cancer cells — or infused back into mice with cancer — and activated with light, the T cells did a better job of killing the cancer cells than they did without the light activation.

In another project, the team engineered a special LED chip to help guide the immune system to tumors. To test this light-activated system, the team used mice with melanoma (skin cancer) on their ears. A tiny battery pack that the mice wore, controlled by the researchers and designed by the School of Chemical Engineering at Sungkyunkwan University in South Korea, sent a wireless signal to the LED chip on the mouse's ears to emit light. By shining light on the tumor and surrounding areas, killer T cells were called to the scene.

Getting cytotoxic T cells to the tumor site was sufficient to overcome the tumor-induced immunosuppression by the T regulatory cells and dramatically improved the results of adoptive T cell transfer in mice.

Light from the current system does not penetrate very far. It can only deliver a functional light signal to the skin or surface of organs. Another drawback of this prototype is that, even though the researchers can switch on the light remotely, the LED needs a wired power source to run.

The team is working on improvements that will make their systems easier to use and applicable to human cancers.

Where Do We Go from Here?

The research team is moving ahead with more studies using light and optics. The University of Rochester has filed for a patent to protect the lab's invention using light-activated algae to control the T cell response to cancer. The researchers hope future studies would help them determine whether the wireless LED signal can deliver light to a tumor deep within the body instead of on the surface.

According to Kim, the technique may be developed further to allow doctors to see if cancer therapy is reaching its target. Right now, a patient has to wait several weeks after receiving immunotherapy, then undergo imaging scans to find out if the treatment worked.

The new method of using light as a cancer treatment is meant to be combined with immunotherapy to make it safer, more T lymphocytes, and traceable. Guiding the T cells to tumors using light solves the problem of getting the immune cells to where they are needed — and overcomes the tumor's control of T regulatory cells that keep cytotoxic T cells away.

"The beauty of our approach is that it's highly flexible, non-toxic, and focused on activating T cells to do their jobs," Kim said in a press release.

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